The intratumoral microbiome in breast cancer: an actionable component of the tumor immune microenvironment.

Breast cancer remains one of the leading causes of cancer-related deaths in women. The discovery of a breast tumor microbiota has deeply changed our understanding of the breast tumor microenvironment, identifying microorganisms as active players in tumor progression. Increasing evidence suggests that intratumoral bacteria may influence multiple hallmarks of breast cancer, including chronic inflammation, immune modulation, metabolic reprogramming, epithelial plasticity, metastatic dissemination, and therapeutic response. Distinct microbial communities have been associated with specific breast cancer subtypes and clinical outcomes, and some mechanistic studies have demonstrated that individual bacterial species and their metabolites can directly regulate oncogenic signaling pathways, reshape the tumor immune microenvironment, and alter sensitivity to chemotherapy and immunotherapy. These findings have generated growing interest in exploiting the breast tumor microbiota as a source of novel diagnostic, prognostic, and predictive biomarkers, as well as a therapeutic target for breast cancer treatment. In this review, we summarize current knowledge on the composition and origin of the breast tumor microbiota, discuss the molecular mechanisms through which tumor-associated microorganisms may influence breast cancer initiation and progression, examine their impact on treatment response, and highlight emerging microbiota-based therapeutic strategies. Finally, we discuss the major technical and biological challenges that currently limit clinical translation, including low microbial biomass, contamination, lack of methodological standardization, and patient-related confounding factors, and outline future perspectives for integrating microbial profiling into precision oncology. A deeper understanding of host-microbe interactions within the breast tumor microenvironment may ultimately enable microbiome-informed approaches for personalized prevention, diagnosis, prognostication, and treatment of breast cancer.